WO2019080983A1 - Novel formulation based on chitosan and method for producing same - Google Patents

Novel formulation based on chitosan and method for producing same

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Publication number
WO2019080983A1
WO2019080983A1 PCT/DZ2018/050010 DZ2018050010W WO2019080983A1 WO 2019080983 A1 WO2019080983 A1 WO 2019080983A1 DZ 2018050010 W DZ2018050010 W DZ 2018050010W WO 2019080983 A1 WO2019080983 A1 WO 2019080983A1
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WO
WIPO (PCT)
Prior art keywords
present
invention according
chitosan
oil
acid
Prior art date
Application number
PCT/DZ2018/050010
Other languages
French (fr)
Inventor
Laribi-Habchi HASSIBA
Khaled LARIBI
Original Assignee
Hassiba Laribi Habchi
Laribi Khaled
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hassiba Laribi Habchi, Laribi Khaled filed Critical Hassiba Laribi Habchi
Publication of WO2019080983A1 publication Critical patent/WO2019080983A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention relates to a process for preparing a therapeutic bio-formulation having a remarkable stability.
  • the present invention relates to a novel bio-formulation useful in therapy, having anti-inflammatory and / or antimicrobial, preservative and healing properties, and particularly a new formulation based on a biopolymer in the form of acetylated chitosan with a degree of acetylation lower than 10% as a cutaneous, anti-microbial and cicatrizing anti-inflammatory active pharmaceutical ingredient and at least one organic acid selected from oxalic acid, acetic acid, lactic acid, ascorbic acid or formic acid), a material waxy, shea butter, active tension and natural oils.
  • the present invention relates to a bio formulation for use in dermatology.
  • the present invention is intended to treat skin inflammation resulting from an allergy as well as that of wounds caused by burns.
  • the present invention also serves to treat microbial infection and to effectively and rapidly heal deep burn wounds.
  • the invention also relates to a process for the preparation of this aforementioned formulation.
  • the invention further relates to a therapeutic topical use of therapeutic treatment using said formulation.
  • the epidermis is made up of three types of cells that are the keranocytes, melanocytes and langerhan cells that play the role in the immune response.
  • the dermis is a connective tissue made up of a fundamental substance in which cells, collagen fibers and elastic fibers bathe. It contains blood and lymphatic vessels and nerves. Apart from its supporting role, the dermis ensures the nutrition of the epidermis (because it is richly vascularized), but also plays a role in the regulation of temperature, pressure and the sensation of pain. It also acts as a water reservoir.
  • the skin is the seat of allergic reactions as observed in the case of contact eczema or atopic eczema.
  • acute skin lesion means the destruction of the part of the skin following a trauma such as deep burn wounds, whether accidental or surgical.
  • Inflammation is a set of biological reactions that occur throughout the animal scale.
  • the inflammation can be localized. It can be defined as the first response to any local aggression by a series of non-specific reactions triggered regardless of the initial cause and are carried out in a few successive stages: vascular, cellulo-vascular and fibrosis-tissue.
  • the signs of inflammation can go as far as a feeling of general malaise and / or an increase in the concentration of certain blood plasma proteins due to fever.
  • Inflammation is a phenomenon followed by a series of local cellular reactions and the release of cytokines and other mediators (histamine, prostaglandins). Inflammation is manifested by an increase in vascular permeability leading to leakage of plasma proteins to the external cellular fluid (leucocytes and macrophages) at the level of inflammation. Whatever the phenomenon envisaged (for example cutaneous discomfort, cutaneous allergies, deep wounds), there is a point common to all these mechanisms which results in the release by the mastocyte, frbroblastic and / or langerhan cells of the skin. at least one mediator of inflammation such as histamine, heparin, prostaglandins, cytokines.
  • the known anti-inflammatories often have significant adverse side effects.
  • the objective of this invention is therefore to be able to have a formulation in the form of a therapeutic cream (skin lesion caused by deep burns or other) based on chitosan as active ingredient associated with other natural products with biological properties following: anti-inflammatory, anti-infectious, healing and restorative of human and animal skin and may not have significant side effects.
  • Chitosan in the form of a hydrochlorinated solution known to have good anti-infectious activity against bacteria, as shown in patent JP 82 137930.
  • chitosan in the treatment of burns by the formation of a film on the surface of the wound of the burned body resistant and permeable to oxygen that will facilitate healing.
  • the object of the present invention is to overcome the disadvantages of the prior art and to propose a bio formulation in the form of a cream having cutaneous anti-inflammatory properties.
  • the present invention also aims to have anti-infectious properties and healing deep wounds burns or other.
  • the object of the present invention is to prepare a cream having preservative properties.
  • An advantage of this invention is to use as an antimicrobial, anti-inflammatory and healing active agent a natural product.
  • One advantage is to use a very abundant and inexpensive preservative.
  • Another advantage is to introduce only a small amount of chitosan into the therapeutic formulation.
  • Another advantage is to prepare an organic formulation in the form of a cream that is stored for a long time at ambient temperatures and in a non-sterile environment (non-hermetic packaging).
  • Chitosan is a polymer derived from chitin that is the component of the exoskeleton of arthropods (insect cuticle or shrimp shell). Chitin is the building block of the cell wall of some yeasts and molds.
  • Chitosan is produced by deacetylation of chitin in an aqueous alkaline medium.
  • the biological antimicrobial activity of the polymer is probably due to its polycationic nature.
  • the amino groups once protonated, interact with the electronegative sites on the surface of the cell of the microorganism which causes a change in the permeability of the cell membrane causing the loss of the intracellular substance. This loss is related to the inhibition of cell growth.
  • the chitosan used according to the present invention may be of various origin. It may be a polymer derived from the deacetylation of chitin from red shrimp, white shrimp, a mixture of red and white shrimp or crabs.
  • the chitosan chosen according to the invention is derived from shrimp shell.
  • the degree of deacetylation that represents the amount of amine groups released the more important it is, the more effective its biological activity.
  • the degree of deacetylation of the chitosan chosen in the present invention is between 70 and 99%.
  • a low molecular weight chitosan has a low biological activity can be compared to the low density of local charges preventing the polymer from interacting effectively with the anionic site on the surface of the cell membrane.
  • Chitosan of low or high molecular weight is not suitable as an antimicrobial agent according to the present invention.
  • the present invention relates to a new bio therapeutic formulation containing chitosan as the active ingredient and natural oils associated with a surfactant.
  • the object of the invention is a new formulation intended to treat cutaneous inflammation resulting from deep burns or eczema.
  • the object of the invention is a new formulation also intended to treat infections of deep cutaneous wounds of burns.
  • the present invention aims at a new formulation with cutaneous healing properties
  • the object of the invention is the use of an inexpensive biodegradable polymer obtained according to the method of its use in the medical and pharmaceutical field, particularly for the preparation of a bioformulation in the form of a cream having biological properties (anti-inflammatory antimicrobial, preservative and healing).
  • the invention relates to a process for preparing a bio-formulation comprising a mixture of organic acid diluted between 0.1 and 3% and a bioplymer, chitosan extracted from a marine biomass in order to prepare a cream, which comprises the steps of :
  • the marine biomass used for the extraction of the polymer is chosen for the availability and the extraction yield among biodegradable marine biomasses such as carapaces of crabs, shells of white shrimps, shells of red shrimp mixture shrimp shells white and red white shrimp. •
  • the amount of biomass in dry matter can reach between 5 and 25 kg to produce between 30 and 70 g of powder of the chitosan polymer.
  • the formulation further comprises an organic acid solution diluted between 0, 1 and 3% in order to ensure the solubility of chitosan;
  • the organic acid is chosen from organic acids, formic acid, oxalic acid, lactic acid and acetic acid.
  • the organic acids are chosen from formic acid, oxalic acid and acetic acid.
  • the formulation further comprises a natural oily phase between 40 and 65% of the total amount of the formulation.
  • the natural oils selected are from soybean oil, sweet almond oil, bitter almond oil, walnut oil, apple oil, carrot oil, walnut oil coconut.
  • the formulation according to the present invention may further comprise as an ingredient of the almond oil conventionally used as a softening and antiseptic of light wounds.
  • the formulation according to the invention may further comprise soybean oil and / or coconut oil as surfactants in order to improve the fluidity of the cream.
  • the formulation according to the present invention may further comprise moisturizing and antiseptic beeswax light wounds.
  • the treatment of the marine biomass chosen before the extraction takes place advantageously at a temperature of 50 - 200 ° C.
  • a mechanical grinding is carried out so as to have a polymer that is easier to solubilize.
  • Purified polymer with a high degree of solubility, a demineralization and deproteinization treatment is carried out under acidic and basic conditions with continuous stirring for a period of 10 to 72 hours.
  • the method of the invention is exceptionally well suited for topical dermal application used in human and animal medicine.
  • compositions according to the present invention are prepared by the usual techniques, depending on the chosen administration form, the desired amounts of organic acid, natural oils being mixed with chitosan, and excipients, in a physiologically acceptable medium.
  • composition of the invention for example in the form of a cream, is preferably applied once or twice a day to the area of the skin requiring treatment for a period of time ranging from a few days to two weeks depending on the severity. of affection. It is especially useful for the treatment of acute traumatic or chronic wounds in humans and animals.
  • a bio-therapeutic cream (anti-inflammatory, anti-infectious, healing) is prepared by the usual techniques by successively mixing the phases containing the components indicated below, the phases A and B being mixed while hot (65 and 80 ° C.).
  • Example 1 A bio-therapeutic cream (anti-inflammatory, anti-infectious, healing) is prepared by the usual techniques by successively mixing the phases containing the components indicated below, the phases A and B being mixed while hot (65 and 80 ° C.).
  • the pH of the cream is adjusted to pH slightly lower than 6 by adding sodium hydroxide
  • the evaluation of the anti-inflammatory activity of the present invention was carried out using the animal-induced paw edema technique of carrageenan. Edema is considered a characteristic sign of inflammation and is an important parameter in the evaluation of anti-inflammatory activity.
  • the clinical study was performed by measuring the weight of the leg of each animal treated with carrageenan. Three lots of animals have five animals per batch. The results obtained are expressed as a percentage of inhibition of edema (equation 1). The results obtained using the present invention showed a very significant degree of inhibition of edema after a period of 4 to 7 days of treatment compared to controls (untreated animals) and animals treated with an anti-inflammatory cream. reference (15 days) (table 1)

Abstract

The present invention relates to a novel formulation in the form of a homogeneous, very time-stable cream made of chitosan in a slightly alkaline aqueous solution with a pH of less than 6, in order to treat the inflammation of deep skin wounds caused by burns or the like. The amount of chitosan introduced into the formualation is between 0.20% and 0.70 % with a molecular weight of between 50 and 100 kDa. Said formulation is in the form of a stable homogeneous cream at room temperature. The invention also relates to a formulation as previously described, characterised in that it can be produced by means of a method comprising at least the following steps: dissolving the chitosan in water by adding acid such as a weak acid, said weak acid advantageously being selected from the group consisting of acetic acid, lactic acid and formic acid; producing an oil phase with natural oils selected from a group containing soybean oil, carrot oil, sweet almond oil, and bitter almond oil; and producing the oil phase at a temperature of between 65 and 80° C. The pH is adjusted preferably at room temperature in order to obtain a creamy solution having a pH greater than 5.

Description

Titre de l'invention  Title of the invention
Nouvelle formulation médicale à base de chitosane et son procédé de préparation  New medical formulation based on chitosan and its preparation process
Domaine technique auquel se rapporte l'invention Technical field to which the invention relates
La présente invention concerne un procédé de préparation d'une bio formulation thérapeutique présentant une stabilité remarquable. La présente invention concerne une nouvelle bio formulation utile en thérapeutique, présentant des propriétés anti inflammatoire et/ou antimicrobienne, conservatrice et cicatrisante, et particulièrement une nouvelle formulation à base d'un biopolymére sous forme de chitosane acétylé avec un degré d'acétylation inférieur à 10 % comme ingrédient pharmaceutique actif anti-inflammatoire cutanée, antimicrobien et cicatrisant et au moins un acide organique choisi parmi l'acide oxalique, l'acide acétique, l'acide lactique, l'acide ascorbique ou l'acide formique) , une matière cireuse, beurre de karité, un tension actif et des huiles naturelles.  The present invention relates to a process for preparing a therapeutic bio-formulation having a remarkable stability. The present invention relates to a novel bio-formulation useful in therapy, having anti-inflammatory and / or antimicrobial, preservative and healing properties, and particularly a new formulation based on a biopolymer in the form of acetylated chitosan with a degree of acetylation lower than 10% as a cutaneous, anti-microbial and cicatrizing anti-inflammatory active pharmaceutical ingredient and at least one organic acid selected from oxalic acid, acetic acid, lactic acid, ascorbic acid or formic acid), a material waxy, shea butter, active tension and natural oils.
La présente invention concerne une formulation bio utilisable en dermatologie. La présente invention destinée à traiter rinflammation cutanée résultant d'une allergie ainsi que celle des plaies causées par des brûlures. La présente invention sert à traiter également l'infection microbienne et à cicatriser efficacement et rapidement les plaies de brûlures profondes. The present invention relates to a bio formulation for use in dermatology. The present invention is intended to treat skin inflammation resulting from an allergy as well as that of wounds caused by burns. The present invention also serves to treat microbial infection and to effectively and rapidly heal deep burn wounds.
L'invention concerne aussi un procédé pour la préparation de cette formulation susmentionnée.  The invention also relates to a process for the preparation of this aforementioned formulation.
L'invention concerne en outre un usage topique pharmaceutique de traitement thérapeutique utilisant la dite formulation. The invention further relates to a therapeutic topical use of therapeutic treatment using said formulation.
Etat de la technique antérieur  State of the prior art
L'épiderme est constitué de trois types de cellules qui sont les kéranocytes, les mélanocytes et les cellules de langerhans qui jouent le rôle dans la réponse immunitaire. The epidermis is made up of three types of cells that are the keranocytes, melanocytes and langerhan cells that play the role in the immune response.
Le derme est un tissu conjonctif constitué d'une substance fondamentale dans laquelle baignent des cellules, des fibres de collagène et des fibres élastiques. Il contient des vaisseaux sanguins et lymphatiques et des nerfs. A part son rôle de soutien, le derme assure la nutrition de l'épiderme (parce qu'il est richement vascularisé), mais aussi joue un rôle dans la régulation de la température, de la pression et de la sensation de douleur. Il assure également un rôle de réservoir en eau.  The dermis is a connective tissue made up of a fundamental substance in which cells, collagen fibers and elastic fibers bathe. It contains blood and lymphatic vessels and nerves. Apart from its supporting role, the dermis ensures the nutrition of the epidermis (because it is richly vascularized), but also plays a role in the regulation of temperature, pressure and the sensation of pain. It also acts as a water reservoir.
La peau est le siège de réactions allergiques telles qu'observées dans le cas d'eczémas de contact ou d'eczémas atopiques.  The skin is the seat of allergic reactions as observed in the case of contact eczema or atopic eczema.
Par lésion cutanée aiguë au sens de l'invention, on entend la destruction de la partie de la peau suite à un traumatisme comme des plaies de brûlures profondes, accidentelles ou chirurgicales.  For the purposes of the invention, the term "acute skin lesion" means the destruction of the part of the skin following a trauma such as deep burn wounds, whether accidental or surgical.
La majorité des bactéries se transforment en bio films, structure membranaire de survie microbienne déviant les facteurs de cicatrisation en créant une inflammation empêchant le processus de défense antimicrobienne d'agir à temps efficacement.  The majority of bacteria are transformed into biofilms, a microbial survival membrane structure that deflects healing factors by creating inflammation that prevents the antimicrobial defense process from acting in time efficiently.
En raison de prise excessive d'antibiotiques, les bactéries ont développé une résistance aux antibiotiques qui limite leur efficacité. Il est donc nécessaire de mettre au point des préparations susceptibles d'agir efficacement contre les microorganismes pathogènes pour l'homme tout en respectant l'homéostasie cutanée et surtout ne favorisant guère la prolifération de souches résistantes.  Due to excessive intake of antibiotics, bacteria have developed antibiotic resistance that limits their effectiveness. It is therefore necessary to develop preparations that can act effectively against pathogenic microorganisms for humans while respecting cutaneous homeostasis and especially not favoring the proliferation of resistant strains.
L'inflammation (ou processus d'inflammation) est un ensemble de réactions biologiques qu'on rencontre dans toute l'échelle animale.  Inflammation (or inflammation process) is a set of biological reactions that occur throughout the animal scale.
L'inflammation peut être localisée. Elle peut se définir comme la première réponse à toute agression locale par une série de réactions non spécifiques déclenchées quelles que soit la cause initiale et s'effectuent en quelques étapes successives : vasculaire, cellulo-vasculaire et fibrosse-tissulaire. The inflammation can be localized. It can be defined as the first response to any local aggression by a series of non-specific reactions triggered regardless of the initial cause and are carried out in a few successive stages: vascular, cellulo-vascular and fibrosis-tissue.
Il existe plusieurs symptômes d'inflammation qui va du sentiment d'inconfort cutané, des démangeaisons au gonflement à la douleur, à la rougeur et à la chaleur. Ces symptômes sont généralement dus à l'inflammation des tissus blessés par un œdème et / ou la vasodilatation des capillaires.  There are several symptoms of inflammation ranging from feeling of skin discomfort, itching, swelling, pain, redness and heat. These symptoms are usually due to inflammation of the tissues injured by edema and / or vasodilatation of the capillaries.
Les signes de rinflammation peuvent aller jusqu'à un sentiment d'un malaise général et /ou une augmentation de la concentration de certaines protéines de plasma sanguin à cause de la fièvre.  The signs of inflammation can go as far as a feeling of general malaise and / or an increase in the concentration of certain blood plasma proteins due to fever.
L'inflammation est un phénomène suivi par une série de réactions cellulaires locales et la libération de cytokines et autres médiateurs (histamine, prostaglandines). L'inflammation se manifeste par une augmentation de la perméabilité vasculaire entraînant une fuite de protéines plasmatiques vers le fluide externe cellulaire (leucocytes et les macrophages) au niveau de Γ inflammation. Quelque soit le phénomène envisagé (par exemple l'inconfort cutané, les allergies cutanées, les blessures profondes), il existe un point commun à tous ces mécanismes qui se traduit par la libération par les cellules mastocytaires, frbroblastiques et / ou langerhans de la peau d'au moins un médiateur de Γ inflammation tel que l'histamine, l'héparine, les prostaglandines, les cytokines. Inflammation is a phenomenon followed by a series of local cellular reactions and the release of cytokines and other mediators (histamine, prostaglandins). Inflammation is manifested by an increase in vascular permeability leading to leakage of plasma proteins to the external cellular fluid (leucocytes and macrophages) at the level of inflammation. Whatever the phenomenon envisaged (for example cutaneous discomfort, cutaneous allergies, deep wounds), there is a point common to all these mechanisms which results in the release by the mastocyte, frbroblastic and / or langerhan cells of the skin. at least one mediator of inflammation such as histamine, heparin, prostaglandins, cytokines.
A cet égard, de nombreuses, de nombreux produits afin de traiter Γ inflammation ont été décrites dans la littérature sous les appellations d'anti-inflammatoire stéroïdiens ou non stéroïdiens.  In this regard, many, many products for treating inflammation have been described in the literature as steroidal or nonsteroidal anti-inflammatory drugs.
Les anti-inflammatoires connus souvent ont des effets secondaires néfastes non négligeables. The known anti-inflammatories often have significant adverse side effects.
A cet effet, la recherche de nouvelles préparations à activité anti -inflammatoire reste nécessaire à développer. For this purpose, the search for new preparations with anti-inflammatory activity remains necessary to develop.
L'objectif de cette présente invention est donc de pouvoir disposer d'une formulation sous forme de crème thérapeutique (lésion cutanée causées par des brûlures profondes ou autres) à base de chitosane comme principe actif associé à d'autres produits naturels présentant des propriétés biologiques suivantes : anti-inflammatoire, anti-infectieuse, cicatrisante et réparatrice de la peau humaine et animale et pouvant ne pas présenter des effets secondaires notables. The objective of this invention is therefore to be able to have a formulation in the form of a therapeutic cream (skin lesion caused by deep burns or other) based on chitosan as active ingredient associated with other natural products with biological properties following: anti-inflammatory, anti-infectious, healing and restorative of human and animal skin and may not have significant side effects.
De nombreux exemples d'utilisation du chitosane ont été cités dan la littérature.  Numerous examples of the use of chitosan have been cited in the literature.
Le chitosane sous forme de solution hydrochlorée, connu d'une bonne activité anti infectieuse envers les bactéries comme le montre le brevet JP 82. 137930.  Chitosan in the form of a hydrochlorinated solution, known to have good anti-infectious activity against bacteria, as shown in patent JP 82 137930.
L'utilisation de chitosane dans le traitement des brûlures par la formation d'un film à la surface de la plaie du corps brûlé résistant et perméable à l'oxygène qui va faciliter la guérison.  The use of chitosan in the treatment of burns by the formation of a film on the surface of the wound of the burned body resistant and permeable to oxygen that will facilitate healing.
Le chitosane utilisé aussi comme agent conservateur de divers produits (Brevet JP 87. 083877).  Chitosan also used as a preservative of various products (Patent JP 87 083877).
Il existe actuellement plusieurs formulations cicatrisantes constituées d'alginate de sodium et de calcium, des pansements à l'acide hyaluronique et des hydrogels, ces préparations même si elles favorisent la cicatrisation en créant un environnement humide, ne possèdent pas de propriétés antimicrobiennes et anti inflammatoires. There are currently several healing formulations consisting of sodium and calcium alginate, hyaluronic acid dressings and hydrogels, these preparations even if they promote healing by creating a moist environment, do not have antimicrobial and anti-inflammatory properties .
Cependant bien que très antibactériens, les pansements à l'argent présentant souvent une cytotoxicité en induisant la mort des cellules qui interviennent dans la cicatrisation des plaies. Egalement les préparations à base d'iode sont non seulement cytotoxiques mais aussi leur activité antimicrobienne diminue en présence de matière organique (fibrine, pus) (Brevet WO 2014131974 Al). However, although very antibacterial, silver dressings often show a cytotoxicity by inducing the death of the cells which intervene in the cicatrization of the wounds. Also the iodine-based preparations are not only cytotoxic but also their antimicrobial activity decreases in the presence of organic matter (fibrin, pus) (Patent WO 2014131974 A1).
La présente invention a pour but de pallier les inconvénients de l'art antérieur et de proposer une bio formulation sous forme de crème ayant des propriétés anti-inflammatoires cutanées.  The object of the present invention is to overcome the disadvantages of the prior art and to propose a bio formulation in the form of a cream having cutaneous anti-inflammatory properties.
La présente invention a pour but également d'avoir des propriétés anti infectieuses et cicatrisantes des plaies profondes de brûlures ou autres.  The present invention also aims to have anti-infectious properties and healing deep wounds burns or other.
La présente invention a pour but de préparer une crème ayant des propriétés de conservation.  The object of the present invention is to prepare a cream having preservative properties.
Un avantage de cette invention est d'utiliser comme agent actif antimicrobien, anti-inflammatoire et cicatrisant un produit naturel.  An advantage of this invention is to use as an antimicrobial, anti-inflammatory and healing active agent a natural product.
Un avantage est d'utiliser un agent conservatoire très abondant et bon marché.  One advantage is to use a very abundant and inexpensive preservative.
Un autre avantage est de n'introduire qu'une faible quantité de chitosane dans la formulation thérapeutique. Another advantage is to introduce only a small amount of chitosan into the therapeutic formulation.
Un autre avantage est de préparer une formulation bio sous forme de crème se conservant longtemps à des températures ambiantes et dans un milieu non stérile (emballage non hermétique). Another advantage is to prepare an organic formulation in the form of a cream that is stored for a long time at ambient temperatures and in a non-sterile environment (non-hermetic packaging).
Le chitosane est un polymère dérivé de la chitine qui représente le composant de l'exosquelette des arthropodes (cuticule de l'insecte ou la carapace de crevettes). La chitine représente l'élément constitutif de la paroi cellulaire de certaines levures et moisissures.  Chitosan is a polymer derived from chitin that is the component of the exoskeleton of arthropods (insect cuticle or shrimp shell). Chitin is the building block of the cell wall of some yeasts and molds.
Le chitosane est produit par déacétylation de la chitine dans un milieu aqueux alcalin. L'activité biologique antimicrobienne du polymère est due probablement à sa nature polycationique. Les groupes aminé une fois protonés, interagissent avec les sites électronégatifs se trouvant à la surface de la cellule du microorganisme ce qui entraine une modification de la perméabilité de la membrane cellulaire en provoquant la perte de la substance intracellulaire. Cette perte est liée à rinhibition de la croissance cellulaire. Chitosan is produced by deacetylation of chitin in an aqueous alkaline medium. The biological antimicrobial activity of the polymer is probably due to its polycationic nature. The amino groups once protonated, interact with the electronegative sites on the surface of the cell of the microorganism which causes a change in the permeability of the cell membrane causing the loss of the intracellular substance. This loss is related to the inhibition of cell growth.
Le chitosane utilisé selon la présente invention peut être d'origine diverse. Il pourra être un polymère issu de la déacétylation de la chitine provenant de crevettes rouges, crevettes blanches, d'un mélange de crevettes rouges et blanches ou de crabes.  The chitosan used according to the present invention may be of various origin. It may be a polymer derived from the deacetylation of chitin from red shrimp, white shrimp, a mixture of red and white shrimp or crabs.
Le chitosane choisi selon l'invention est issu de la carapace de crevettes. The chitosan chosen according to the invention is derived from shrimp shell.
Le degré de déacétylation qui représente la quantité de groupes aminés libérés, plus il est important, plus son activité biologique est efficace.  The degree of deacetylation that represents the amount of amine groups released, the more important it is, the more effective its biological activity.
Le degré de déacétylation du chitosane choisi dans la présente invention est compris entre 70 et 99%. The degree of deacetylation of the chitosan chosen in the present invention is between 70 and 99%.
Nous avons remarqué qu'un chitosane de faible poids moléculaire possède une faible activité biologique peut être par rapport à la faible densité de charges locales empêchant le polymère d'interagir efficacement avec le site anionique à la surface de la membrane cellulaire.  We have noticed that a low molecular weight chitosan has a low biological activity can be compared to the low density of local charges preventing the polymer from interacting effectively with the anionic site on the surface of the cell membrane.
Nous avons constaté également qu'un haut poids moléculaire du chitosane diminue son activité biologique cela est dû probablement à une modification moléculaire du polymère. L'interaction électrostatique du chitosane et la surface de la membrane cellulaire peut être limitée.  We have also found that a high molecular weight of chitosan decreases its biological activity this is probably due to a molecular modification of the polymer. The electrostatic interaction of chitosan and the surface of the cell membrane can be limited.
Le chitosane de faible ou de haut poids moléculaire n'est pas adéquat comme agent antimicrobien selon la présente invention. Chitosan of low or high molecular weight is not suitable as an antimicrobial agent according to the present invention.
But de l'invention  Purpose of the invention
La présente invention concerne une nouvelle bio formulation thérapeutique contenant du chitosane comme principe actif et des huiles naturelles associé à un tensioactif.  The present invention relates to a new bio therapeutic formulation containing chitosan as the active ingredient and natural oils associated with a surfactant.
L'invention a pour objectif une nouvelle formulation destinée à traiter l'inflammation cutanée issue de brûlures profondes ou d'eczéma.  The object of the invention is a new formulation intended to treat cutaneous inflammation resulting from deep burns or eczema.
L'invention a pour but une nouvelle formulation destinée également à traiter les infections des plaies cutanées profondes de brûlures.  The object of the invention is a new formulation also intended to treat infections of deep cutaneous wounds of burns.
La présente invention a pour objectif une nouvelle formulation à des propriétés de cicatrisation cutanéeThe present invention aims at a new formulation with cutaneous healing properties
L'invention a pour but l'utilisation d'un polymère biodégradable bon marché obtenu selon le procédé de son usage dans le domaine médical, pharmaceutique, particulièrement pour la préparation d'une bioformulation sous forme de crème ayant des propriétés biologiques (anti-inflammatoire, antimicrobienne, conservatrice et cicatrisante). The object of the invention is the use of an inexpensive biodegradable polymer obtained according to the method of its use in the medical and pharmaceutical field, particularly for the preparation of a bioformulation in the form of a cream having biological properties (anti-inflammatory antimicrobial, preservative and healing).
Présentation de la molécule d'invention Presentation of the invention molecule
L'invention concerne un procédé de préparation d'une bio formulation comprenant un mélange d'acide organique dilué entre 0,1 et 3 % et un bioplymére, chitosane extrait d'une biomasse marine afin de préparer une crème, qui comprend les étapes de :  The invention relates to a process for preparing a bio-formulation comprising a mixture of organic acid diluted between 0.1 and 3% and a bioplymer, chitosan extracted from a marine biomass in order to prepare a cream, which comprises the steps of :
• Application cutanée sur la peau humaine  • Skin application on human skin
· Utilisation d'une faible quantité du polymère dans la préparation comprise entre 0,3 et 0, 7 % · Use of a small amount of the polymer in the preparation of 0.3 to 0.7%
• Dans un mode de réalisation, la biomasse marine utilisée pour l'extraction du polymère est choisie pour la disponibilité et le rendement d'extraction parmi les biomasses marines biodégradables telles que les carapaces de crabs, carapaces de crevettes blanches, carapaces de crevettes rouges mélange de carapaces de crevettes blanches et rouges de crevettes blanches. • La quantité de biomasse en matière sèche peut atteindre entre 5 et 25 kg pour produire entre 30 et 70 g de poudre du polymère chitosane. • In one embodiment, the marine biomass used for the extraction of the polymer is chosen for the availability and the extraction yield among biodegradable marine biomasses such as carapaces of crabs, shells of white shrimps, shells of red shrimp mixture shrimp shells white and red white shrimp. • The amount of biomass in dry matter can reach between 5 and 25 kg to produce between 30 and 70 g of powder of the chitosan polymer.
Dans un mode de réalisation, la formulation comprend en outre une solution d'acide organique diluée entre 0, 1 et 3% afin d'assurer la solubilité du chitosane ; l'acide organique est choisi parmi les acides organiques, acide formique, acide oxalique, acide lactique, acide acétique.  In one embodiment, the formulation further comprises an organic acid solution diluted between 0, 1 and 3% in order to ensure the solubility of chitosan; the organic acid is chosen from organic acids, formic acid, oxalic acid, lactic acid and acetic acid.
De préférence les acides organiques sont choisis parmi l'acide formique, acide oxalique, acide acétique.  Preferably, the organic acids are chosen from formic acid, oxalic acid and acetic acid.
Selon la présente invention, la formulation comprend en outre une phase l'huileuse naturelle entre 40 et 65% de la quantité totale de la formulation. Les huiles naturelles choisies sont parmi l'huile de soja, l'huile d'amande douce, l'huile d'amande amère, l'huile de noix, l'huile de pomme, l'huile de carotte, huile de noix de coco. La formulation selon la présente invention peut comprendre en outre comme ingrédient de l'huile d'amande utilisée classiquement comme adoucissant et antiseptique des plaies légères.  According to the present invention, the formulation further comprises a natural oily phase between 40 and 65% of the total amount of the formulation. The natural oils selected are from soybean oil, sweet almond oil, bitter almond oil, walnut oil, apple oil, carrot oil, walnut oil coconut. The formulation according to the present invention may further comprise as an ingredient of the almond oil conventionally used as a softening and antiseptic of light wounds.
La formulation selon l'invention peut en outre comprendre de l'huile de soja et / ou l'huile de noix de coco comme tensioactifs afin d'améliorer la fluidité de la crème.  The formulation according to the invention may further comprise soybean oil and / or coconut oil as surfactants in order to improve the fluidity of the cream.
La formulation selon la présente invention peut en outre comprendre de la cire d'abeille hydratante et antiseptique des blessures légères.  The formulation according to the present invention may further comprise moisturizing and antiseptic beeswax light wounds.
Le traitement de la biomasse marine choisie avant l'extraction a lieu avantageusement à une température de 50 - 200°C.  The treatment of the marine biomass chosen before the extraction takes place advantageously at a temperature of 50 - 200 ° C.
Dans le cas où la biomasse marine choisie est riche en sels minéraux, lipides et protéines, on procède à un broyage par voie mécanique de façon à avoir un polymère plus facile à solubiliser.  In the case where the marine biomass chosen is rich in mineral salts, lipids and proteins, a mechanical grinding is carried out so as to have a polymer that is easier to solubilize.
Polymère purifié avec un degré de solubilité important, on effectue un traitement de déminéralisation et de déprotéinisation dans des conditions acides et basiques sous agitation continue durant une période de 10 à 72h. Purified polymer with a high degree of solubility, a demineralization and deproteinization treatment is carried out under acidic and basic conditions with continuous stirring for a period of 10 to 72 hours.
Mode de réalisation de l'invention  Embodiment of the invention
Le procédé d'invention convient exceptionnellement bien à une application dermique topique utilisée en médecine humaine et animale.  The method of the invention is exceptionally well suited for topical dermal application used in human and animal medicine.
Les compositions conformes à la présente invention sont préparées par les techniques usuelles, en fonction de la forme d'administration choisie, les quantités voulues d'acide organique, des huiles naturelles étant mélangées avec le chitosane, et excipients, dans un milieu physiologiquement acceptable. The compositions according to the present invention are prepared by the usual techniques, depending on the chosen administration form, the desired amounts of organic acid, natural oils being mixed with chitosan, and excipients, in a physiologically acceptable medium.
La composition de l'invention, par exemple sous forme de crème, est appliquée de préférence une à deux fois par jour sur la zone de la peau nécessitant le traitement, pendant une période de temps pouvant aller de quelques jours à deux semaine suivant la gravité de l'affection. Elle est tout particulièrement utile pour le traitement des plaies aiguës traumatiques ou chroniques chez l'homme et chez des animaux. The composition of the invention, for example in the form of a cream, is preferably applied once or twice a day to the area of the skin requiring treatment for a period of time ranging from a few days to two weeks depending on the severity. of affection. It is especially useful for the treatment of acute traumatic or chronic wounds in humans and animals.
Les exemples suivants illustrent l'invention plus en détail sans en limiter la portée. Dans tous les exemples de compositions qui suivent, les parties sont exprimées en poids, sauf indication contraire.  The following examples illustrate the invention in more detail without limiting its scope. In all of the following examples of compositions, parts are by weight unless otherwise indicated.
On prépare une crème bio thérapeutique (anti-inflammatoire, anti infectieuse, cicatrisante) par les techniques usuelles en mélangeant successivement les phases contenant les composants indiqués ci-après, les phases A et B étant mélangées à chaud (65 et 80 °C). Exemple 1 A bio-therapeutic cream (anti-inflammatory, anti-infectious, healing) is prepared by the usual techniques by successively mixing the phases containing the components indicated below, the phases A and B being mixed while hot (65 and 80 ° C.). Example 1
Phase A  Phase A
Acide acétique (0,1 - 3%)  Acetic acid (0.1 - 3%)
- Chitosane (0,30 - 100 g)  - Chitosan (0.30 - 100 g)
- Eau (45 -100 ml)  - Water (45 -100 ml)
Phase B  Phase B
L'huile d'amande amère (20 - 30 ml)  Bitter almond oil (20 - 30 ml)
Beurre de karité (18 - 35 g)  Shea butter (18 - 35 g)
lécithine de soja (0,2 -1 ml)  soy lecithin (0.2-1 ml)
- l'huile de pomme (4 - 8 ml)  - apple oil (4 - 8 ml)
cire d'abeille (3 - 6 g)  beeswax (3 - 6 g)
Le pH de la crème est ajusté à pH légèrement inférieur à 6 par addition de la soude  The pH of the cream is adjusted to pH slightly lower than 6 by adding sodium hydroxide
Exemple 2 Example 2
Phase A Phase A
· l'huile d'amande douce (24 - 30 ml) · Sweet almond oil (24 - 30 ml)
• l'huile d'amande amère (15 - 40 ml)  • bitter almond oil (15 - 40 ml)
• l'huile de ricin (2 - 7 ml)  • castor oil (2 - 7 ml)
Phase B  Phase B
· cire d'abeille (2 - 8 g) · Beeswax (2 - 8 g)
• chitosane (0,20- 0,70g)  • chitosan (0.20-0.70g)
Résultats obtenus Results obtained
• Test d'anti-inflammatoire  • Anti-inflammatory test
L'évaluation de l'activité anti-inflammatoire de la présente invention a été réalisée en utilisant la technique d' œdème induit au niveau de patte de l'animal par la carraghenane. Un œdème est considéré comme un signe caractéristique d'inflammation et représente un paramètre important dans l'évaluation de l'activité anti- inflammatoire. The evaluation of the anti-inflammatory activity of the present invention was carried out using the animal-induced paw edema technique of carrageenan. Edema is considered a characteristic sign of inflammation and is an important parameter in the evaluation of anti-inflammatory activity.
L'étude clinique a été réalisée par la mesure du poids de la patte de chaque animal traité par la carraghenane. Trois lots d'animaux a raison de cinq animal par lot. Les résultats obtenus sont exprimés par un pourcentage d'inhibition d'œdème (équation 1). Les résultats obtenus en utilisant la présente invention ont montré un taux d'inhibition d'œdème très significatif après un temps de 4 à 7 jours de traitement par rapport aux témoins (animaux non traités) et aux animaux traités par une crème anti-inflammatoire de référence (15 jours) (tableau 1)  The clinical study was performed by measuring the weight of the leg of each animal treated with carrageenan. Three lots of animals have five animals per batch. The results obtained are expressed as a percentage of inhibition of edema (equation 1). The results obtained using the present invention showed a very significant degree of inhibition of edema after a period of 4 to 7 days of treatment compared to controls (untreated animals) and animals treated with an anti-inflammatory cream. reference (15 days) (table 1)
„. ... . .. .t. % d oedème lot témoin-% d oedème lot trait ... ". ... .. t . % edema batch control-% edema batch trait ...
% d inhibition = ; xlOO (1)  % inhibition =; xlOO (1)
%d oedème lot témoin Tableau 1 : Pourcentage d'inhibition des œdèmes % edema batch control Table 1: Percentage of edema inhibition
Figure imgf000007_0002
Figure imgf000007_0002
Test anti-infectieux (test de cicatrisation)  Anti-infective test (scarring test)
•S Afin d'étudier l'effet cicatrisant de la présente invention et de le comparé a d'autre produits connues comme de bons cicatrisants , un test a été réalisé sur des rats de laboratoire et qui consiste à faire brûler volontairement sur trois lots de rats à raison de 5 rats par lot afin de provoquer des plaies profondes , puis d'appliquer des divers produits et suivre l'évolution de la guérison tout en mesurant les surfaces des plaies calculées par ordinateur à l'aide du logiciel AUTOCAD sur des périodes bien déterminées. Les résultats obtenus par application cutanée de la présente invention ont montré une nette diminution de surfaces des plaies après 7 jours de traitement par rapport au lot témoin (non traité) et au lot traité par deux crèmes cicatrisantes de référence. S • To study the healing effect of the present invention and a comparative other products known as good healing, a test was conducted on laboratory rats and that is to voluntarily burn three batches rats at a rate of 5 rats per batch to cause deep wounds, then apply various products and monitor the progress of healing while measuring computer-calculated wound surfaces using AUTOCAD software over periods well determined. The results obtained by dermal application of the present invention showed a clear decrease in wound areas after 7 days of treatment compared to the control batch (untreated) and to the batch treated with two reference healing creams.
Les résultats de cet essai sont regroupés dans le Tableau 2  The results of this test are summarized in Table 2
Tableau 2 : Résultats du test cicatrisant Table 2: Healing Test Results
Figure imgf000007_0001
Figure imgf000007_0001

Claims

Revendications  claims
1. La présente invention destinée à traiter l'inflamniation due aux plaies cutanées profondes causées par des brûlures ou autres, caractérisées en ce qu'elle renferme du chitosane, des huiles naturelles, de la cire d'abeille, un tensioactif et au moins un acide organique choisi dans le groupe constitué par l'acide oxalique, acide formique et l'acide acétique.  The present invention is intended to treat inflamniation due to deep skin wounds caused by burns or the like, characterized in that it contains chitosan, natural oils, beeswax, a surfactant and at least one organic acid selected from the group consisting of oxalic acid, formic acid and acetic acid.
2. La présente invention selon la revendication 1 destinée à traiter l'infection microbienne et à cicatriser les plaies profondes , caractérisées en ce qu'elle renferme du chitosane, des huiles naturelles, de la cire d'abeille, un tensioactif et au moins un acide organique choisi dans le groupe constitué par l'acide oxalique, acide formique et l'acide acétique.  2. The present invention according to claim 1 for treating microbial infection and healing deep wounds, characterized in that it contains chitosan, natural oils, beeswax, a surfactant and at least one organic acid selected from the group consisting of oxalic acid, formic acid and acetic acid.
3. La présente invention selon les revendications 1 et 2, caractérisée en ce que le chitosane issu de la chitine de crevette.  3. The present invention according to claims 1 and 2, characterized in that the chitosan derived from shrimp chitin.
4. La présente invention selon les revendications 1 à 3, caractérisée en ce que le chitosane provient de la N - désacétylation de la chitine.  4. The present invention according to claims 1 to 3, characterized in that the chitosan comes from the N-deacetylation of chitin.
5. La présente invention selon les revendications 1 à 4, caractérisée en ce que le chitosane présente un degré de déacétylation compris entre 70 et 99%.  5. The present invention according to claims 1 to 4, characterized in that the chitosan has a degree of deacetylation of between 70 and 99%.
6. La présente invention selon la revendication 4, caractérisée en ce que le chitosane un degré d'acétylation inférieur à 10%.  6. The present invention according to claim 4, characterized in that chitosan has a degree of acetylation of less than 10%.
7. La présente invention selon les revendications 3 à 6 caractérisée en ce que le chitosane présente un poids moléculaire compris entre 50 et 100 KDa.  7. The present invention according to claims 3 to 6 characterized in that the chitosan has a molecular weight of between 50 and 100 KDa.
8. La présente invention selon les revendications 1 et 2, caractérisée en ce que les huiles naturelles sont choisies parmi l'huile de pomme, l'huile d'amande amère, l'huile d'amande douce, l'huile de ricin, l'huile de soja, l'huile de carotte l'huile de noix, l'huile de noix de coco.  8. The present invention according to claims 1 and 2, characterized in that the natural oils are chosen from apple oil, bitter almond oil, sweet almond oil, castor oil, soybean oil, carrot oil, walnut oil, coconut oil.
9. La présente invention selon la revendication 8, caractérisée en ce que le tensioactif est la lécithine se soja, Coco-bedaine, Coco-glucoside.  9. The present invention according to claim 8, characterized in that the surfactant is lecithin soy, Coco-belly, coco-glucoside.
10. La présente invention selon les revendications 1 et 2, caractérisée en une formulation sous forme de crème pour application thérapeutique et / ou pharmaceutique.  10. The present invention according to claims 1 and 2, characterized in a cream formulation for therapeutic and / or pharmaceutical application.
11. La présente invention selon la revendication 8, caractérisée en ce que la crème préparée traite l'inflammation des plaies profondes causées par des brûlures cutanées du deuxième et troisième degré.  11. The present invention according to claim 8, characterized in that the prepared cream treats inflammation of deep wounds caused by second and third degree skin burns.
12. La présente invention selon les revendications 9, et 10 caractérisée en ce que la crème préparée traite les infections microbiennes.  The present invention according to claims 9, and characterized in that the prepared cream treats microbial infections.
13. La présente invention selon la revendication 9, caractérisée en ce que la crème préparée cicatrise rapidement et efficacement les plaies profondes causées par des brûlures cutanées ou accidentelles.  13. The present invention according to claim 9, characterized in that the prepared cream heals rapidly and effectively the deep wounds caused by skin burns or accidental.
14. La présente invention selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle comprend en outre des parfums nuturels.  14. The present invention according to any one of the preceding claims, characterized in that it further comprises nuturels fragrances.
15. La présente invention selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle comprend en outre la cire d'abeille.  15. The present invention as claimed in any one of the preceding claims, characterized in that it further comprises beeswax.
16. La présente invention selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle comprend un acide organique dilué entre 0,01 et 3%  16. The present invention according to any one of the preceding claims, characterized in that it comprises an organic acid diluted between 0.01 and 3%.
17. La présente invention selon les revendications 1 à 7, caractérisée en ce qu'elle comprend un chitosane sous forme de poudre ayant une granulométrie inférieure à 150 microns.  17. The present invention according to claims 1 to 7, characterized in that it comprises a chitosan in powder form having a particle size less than 150 microns.
18. La présente invention selon la revendication 17, caractérisée en ce qu'elle comprend une poudre de chitosane avec une granulométrie inférieur à 120 microns. 18. The present invention according to claim 17, characterized in that it comprises a chitosan powder with a particle size less than 120 microns.
19. La présente invention selon la revendication 10, caractérisée en ce qu'elle comprend une phase l'huileuse comprise entre 40 et 65%. 19. The present invention according to claim 10, characterized in that it comprises an oily phase of between 40 and 65%.
20. La présente invention selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle est présentée sous forme pour application topique externe.  20. The present invention according to any one of the preceding claims, characterized in that it is presented in form for external topical application.
21. La présente invention selon l'une quelconque des revendications précédentes, caractérisée en ce qu'elle comprend en outre un ou plusieurs actifs secondaires choisis parmi un agent cicatrisant, un anti-inflammatoire, un anti-infectieux et une vitamine telle que la vitamine A, B et E .  21. The present invention according to any one of the preceding claims, characterized in that it further comprises one or more secondary active agents chosen from a healing agent, an anti-inflammatory, an anti-infectious and a vitamin such as vitamin A, B and E.
23. La présente invention selon les revendications de 1 à 8, caractérisée en ce qu'elle comprend les additifs naturels thérapeutiques et/ ou pharmaceutiques acceptables, tels que les parfums, les conservateurs, les vitamines, les agents antibactériens, antiseptiques, les agents antifongiques, antidouleurs, les anti- inflammatoires, les agents favorisants la cicatrisation, les agents hydratants.  23. The present invention according to claims 1 to 8, characterized in that it comprises acceptable natural therapeutic and / or pharmaceutical additives, such as perfumes, preservatives, vitamins, antibacterial agents, antiseptics, antifungal agents , painkillers, anti-inflammatories, agents promoting healing, moisturizing agents.
24. Méthode de traitement thérapeutique et /ou pharmaceutique de la peau comprenant au moins une apphcation de la présente invention selon l'une des revendications 1 à 10 sur des plaies cutanées profondes toutes les 24 heures en vue d'accélérer la cicatrisation et d'améliorer l'apparence de la peau. 24. A method of therapeutic and / or pharmaceutical treatment of the skin comprising at least one apphcation of the present invention according to one of claims 1 to 10 on deep skin wounds every 24 hours to accelerate healing and to improve the appearance of the skin.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114949021A (en) * 2022-05-28 2022-08-30 广西医科大学 A skin repairing medicine containing chicken fat extract

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4303415A1 (en) * 1993-02-05 1994-08-11 Adolf Riedl Emulsion containing chitosan
DE10148302A1 (en) * 2001-09-29 2003-04-17 Beiersdorf Ag Solid water/oil emulsion, used as moisturizing, anti-wrinkle, anti-acne, cleansing, sun protection, after-sun, lip salve or decorative cosmetic stick contains oil, wax, moisturizer in aqueous phase and emulsifier
WO2014126370A1 (en) * 2013-02-13 2014-08-21 Dong-A Pharmaceutical Co.,Ltd Film-forming pharmaceutical composition for wound healing and method for preparing the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4303415A1 (en) * 1993-02-05 1994-08-11 Adolf Riedl Emulsion containing chitosan
DE10148302A1 (en) * 2001-09-29 2003-04-17 Beiersdorf Ag Solid water/oil emulsion, used as moisturizing, anti-wrinkle, anti-acne, cleansing, sun protection, after-sun, lip salve or decorative cosmetic stick contains oil, wax, moisturizer in aqueous phase and emulsifier
WO2014126370A1 (en) * 2013-02-13 2014-08-21 Dong-A Pharmaceutical Co.,Ltd Film-forming pharmaceutical composition for wound healing and method for preparing the same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114949021A (en) * 2022-05-28 2022-08-30 广西医科大学 A skin repairing medicine containing chicken fat extract

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